Poly(triazolyl methacrylate) glycopolymers as potential targeted unimolecular nanocarriers

© The Royal Society of Chemistry 2019.Synthetic glycopolymers are increasingly investigated as multivalent ligands for a range of biological and biomedical applications. This study indicates that glycopolymers with a fine-tuned balance between hydrophilic sugar pendant units and relatively hydrophobic polymer backbones can act as single-chain targeted nanocarriers for low molecular weight hydrophobic molecules. Non-covalent complexes formed from poly(triazolyl methacrylate) glycopolymers and low molecular weight hydrophobic guest molecules were characterised through a range of analytical techniques-DLS, SLS, TDA, fluorescence spectroscopy, surface tension analysis-and molecular dynamics (MD) modelling simulations provided further information on the macromolecular characteristics of these single chain complexes. Finally, we show that these nanocarriers can be utilised to deliver a hydrophobic guest molecule, Nile red, to both soluble and surface-immobilised concanavalin A (Con A) and peanut agglutinin (PNA) model lectins with high specificity, showing the potential of non-covalent complexation with specific glycopolymers in targeted guest-molecule delivery.Peer reviewedFinal Published versio

The Effect of Lattice Vibrations on Substitutional Alloy Thermodynamics

A longstanding limitation of first-principles calculations of substitutional alloy phase diagrams is the difficulty to account for lattice vibrations. A survey of the theoretical and experimental literature seeking to quantify the impact of lattice vibrations on phase stability indicates that this effect can be substantial. Typical vibrational entropy differences between phases are of the order of 0.1 to 0.2 k_B/atom, which is comparable to the typical values of configurational entropy differences in binary alloys (at most 0.693 k_B/atom). This paper describes the basic formalism underlying ab initio phase diagram calculations, along with the generalization required to account for lattice vibrations. We overview the various techniques allowing the theoretical calculation and the experimental determination of phonon dispersion curves and related thermodynamic quantities, such as vibrational entropy or free energy. A clear picture of the origin of vibrational entropy differences between phases in an alloy system is presented that goes beyond the traditional bond counting and volume change arguments. Vibrational entropy change can be attributed to the changes in chemical bond stiffness associated with the changes in bond length that take place during a phase transformation. This so-called ``bond stiffness vs. bond length'' interpretation both summarizes the key phenomenon driving vibrational entropy changes and provides a practical tool to model them.Comment: Submitted to Reviews of Modern Physics 44 pages, 6 figure

Evidence of a new state in 11^{11}Be observed in the 11^{11}Li β\beta-decay

Coincidences between charged particles emitted in the $\beta$-decay of $^{11}$Li were observed using highly segmented detectors. The breakup channels involving three particles were studied in full kinematics allowing for the reconstruction of the excitation energy of the $^{11}$Be states participating in the decay. In particular, the contribution of a previously unobserved state at 16.3 MeV in $^{11}$Be has been identified selecting the $\alpha$ + $^7$He$\to\alpha$ + $^6$He+n channel. The angular correlations between the $\alpha$ particle and the center of mass of the $^6$He+n system favors spin and parity assignment of 3/2$^-$ for this state as well as for the previously known state at 18 MeV.Comment: 13 pages, 6 figure

Evaluation of enzymatic extract with lipase activity of yarrowia lipolytica. an application of data mining for the food industry wastewater treatment

The object of this research was to obtain the Crude Enzymatic Extract (CEE) of Yarrowia lipolytica ATCC 9773, in the medium of 30% Water of Sales (SW) applying a biologically treatment to three different concentrations yeast inoculum food wastewater, collected from cheese and whey production. It was evaluated the behavior of the inoculum in a suitable medium that stimulates lipids biodegradation. The standard liquid-liquid partition method SM 5520 B was used to quantify fat and oil removal for each concentration of yeast, before treatment and post treatment. The Industrial Fat effluent was characterized by physical chemical patterns, and two treatments were evaluated; Treatment 1 consisted of pH 5.0 and treatment 2 with a pH of 6.5, both with the following characteristics; Concentration of inoculum 8% 12% and 16% at 27Â °C temperature and evaluation time 32Â h. The best results (2.702Â mg/L fat and 83% degradation oil) were found to be pH 5.0, 16% concentration and 27Â °C, BOD5, and COD decreased by 43.07% and 44.35%, respectively during the 32Â h; For pH 6.5, 8% concentration at 32Â h and at room temperature, degraded 2.177Â mg/L fat and oil (67% degradation); The BOD5, and COD decreased by 37.93% and 39.19%, in the same time span. The treatment at pH 5.0 inoculum concentration of 16% was effective in removing 83% of the volume of fats and oil in the effluent, representing a useful tool for the wastewater treatment

A randomized clinical trial indicates that levamisole increases the time to relapse in children with steroid-sensitive idiopathic nephrotic syndrome

Levamisole has been considered the least toxic and least expensive steroid-sparing drug for preventing relapses of steroid-sensitive idiopathic nephrotic syndrome (SSINS). However, evidence for this is limited as previous randomized clinical trials were found to have methodological limitations. Therefore, we conducted an international multicenter, placebo-controlled, double-blind, randomized clinical trial to reassess its usefulness in prevention of relapses in children with SSINS. The efficacy and safety of one year of levamisole treatment in children with SSINS and frequent relapses were evaluated. The primary analysis cohort consisted of 99 patients from 6 countries. Between 100 days and 12 months after the start of study medication, the time to relapse (primary endpoint) was significantly increased in the levamisole compared to the placebo group (hazard ratio 0.22 [95% confidence interval 0.11-0.43]). Significantly, after 12 months of treatment, six percent of placebo patients versus 26 percent of levamisole patients were still in remission. During this period, the most frequent serious adverse event (four of 50 patients) possibly related to levamisole was asymptomatic moderate neutropenia, which was reversible spontaneously or after treatment discontinuation. Thus, in children with SSINS and frequent relapses, levamisole prolonged the time to relapse and also prevented recurrence during one year of treatment compared to prednisone alone. However, regular blood controls are necessary for safety issues

Insights into the influence of the cooling profile on the reconstitution times of amorphous lyophilized protein formulations

Lyophilized protein formulations must be reconstituted back into solution prior to patient administration and in this regard long reconstitution times are not ideal. The factors that govern reconstitution time remain poorly understood. The aim of this research was to understand the influence of the lyophilization cooling profile (including annealing) on the resulting cake structure and reconstitution time. Three protein formulations (BSA 50 mg/ml, BSA 200 mg/ml and IgG1 40 mg/ml, all in 7% w/v sucrose) were investigated after cooling at either 0.5 °C/min, or quench cooling with liquid nitrogen with/without annealing. Significantly longer reconstitution times were observed for the lower protein concentration formulations following quench cool. Porosity measurements found concomitant increases in the surface area of the porous cake structure but a reduction in total pore volume. We propose that slow reconstitution results from either closed pores or small pores impeding the penetration of water into the lyophilized cake

In vitro digestion and lactase treatment influence uptake of quercetin and quercetin glucoside by the Caco-2 cell monolayer

BACKGROUND: Quercetin and quercetin glycosides are widely consumed flavonoids found in many fruits and vegetables. These compounds have a wide range of potential health benefits, and understanding the bioavailability of flavonoids from foods is becoming increasingly important. METHODS: This study combined an in vitro digestion, a lactase treatment and the Caco-2 cell model to examine quercetin and quercetin glucoside uptake from shallot and apple homogenates. RESULTS: The in vitro digestion alone significantly decreased quercetin aglycone recovery from the shallot digestate (p < 0.05), but had no significant effect on quercetin-3-glucoside recovery (p > 0.05). Digestion increased the Caco-2 cell uptake of shallot quercetin-4'-glucoside by 2-fold when compared to the non-digested shallot. Despite the loss of quercetin from the digested shallot, the bioavailability of quercetin aglycone to the Caco-2 cells was the same in both the digested and non-digested shallot. Treatment with lactase increased quercetin recovery from the shallot digestate nearly 10-fold and decreased quercetin-4'-glucoside recovery by more than 100-fold (p < 0.05), but had no effect on quercetin recovery from apple digestates. Lactase treatment also increased shallot quercetin bioavailability to the Caco-2 cells approximately 14-fold, and decreased shallot quercetin-4'-glucoside bioavailability 23-fold (p < 0.05). These Caco-2 cells had lactase activity similar to that expressed by a lactose intolerant human. CONCLUSIONS: The increase in quercetin uptake following treatment with lactase suggests that dietary supplementation with lactase may increase quercetin bioavailability in lactose intolerant humans. Combining the digestion, the lactase treatment and the Caco-2 cell culture model may provide a reliable in vitro model for examining flavonoid glucoside bioavailability from foods

Ambiguity Measures for preference-based decision viwewpoints

This paper examines the ambiguity of subjective judgments, which are represented by a system of pairwise preferences over a given set of alternatives. Such preferences are valued with respect to a set of reasons, in favor and against the alternatives, establishing a complete judgment, or viewpoint, on how to solve the decision problem. Hence, viewpoints entail particular decisions coming from the system of preferences, where the preference-based reasoning of a given viewpoint holds according to its soundness or coherence. Here we explore such a coherence under the frame of ambiguity measures, aiming at learning viewpoints with highest preference-score and minimum ambiguity. We extend existing measures of ambiguity into a multi-dimensional fuzzy setting, and suggest some future lines of research towards measuring the coherence or (ir)rationality of viewpoints, exploring the use of information measures in the context of preference learning

GATE : a simulation toolkit for PET and SPECT

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols, and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at the address http://www-lphe.epfl.ch/GATE/